And Neck Tumors (and + neck_tumor)

Distribution by Scientific Domains

Kinds of And Neck Tumors

  • head and neck tumor


  • Selected Abstracts


    111Indium Pentetreotide Imaging in the Evaluation of Head and Neck Tumors

    THE LARYNGOSCOPE, Issue 10 2005
    David Myssiorek MD
    Abstract Objectives/Hypothesis: Peptide receptor imaging with 111Indium pentetreotide is useful in the diagnosis of diffuse neuroendocrine system tumors (DNEST) of the head and neck. Uses of 111Indium pentetreotide scintigraphy include tumor and metastases detection, familial tumor screening, and surveillance for recurrence. Using target to background ratios (TBR) could generate a comparative scale for these tumors. Study Design: A retrospective study evaluated the size, TBR, conventional imaging, and outcomes of patients imaged with 111Indium pentetreotide scintigraphy for suspected head and neck DNEST. Methods: Patients with head and neck tumors imaged by 111Indium pentetreotide scintigraphy during a nine-year period were reviewed. Data analyzed were age, sex, scintigraphy, pathology, and conventional radiology. Tumor data included dimension, multiplicity, metastases, and tumor and brain counts. Results: Fifty-three patients underwent 58 scans. The sensitivity and specificity were 93% and 92%. Several different DNEST were successfully evaluated, including familial paragangliomas and multiple paragangliomas. TBRs were variable depending on type of DNEST. Conclusions:111Indium pentetreotide scintigraphy is accurate in determining the presence of paragangliomas, carcinoid tumors, esthesioneuroblastomas, small cell neuroendocrine tumors, andmetastases. It is an excellent surveillance tool. Screening patients for familial paragangliomas can be accomplished. No reliable comparative scale to distinguish amongst the various DNEST could be developed using TBR. [source]


    Expression of the Extra Domain B of Fibronectin, a Marker of Angiogenesis, in Head and Neck Tumors,

    THE LARYNGOSCOPE, Issue 7 2003
    Manfred T. Birchler MD
    Abstract Objectives/Hypothesis The extra domain B (ED-B) of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is expressed in the majority of aggressive solid human tumors, whereas it is not detectable in normal vessels and tissues. Study Design In view of the diagnostic and therapeutic clinical applications of the L19 antibody, which is specific for the ED-B domain of fibronectin, a prospective immunohistochemical analysis of different head and neck tumors was performed. Methods In all, 82 head and neck tissue biopsy specimens were immunohistochemically analyzed using the L19 antibody. They consisted of 53 different malignant tumors, 8 benign tumors, 10 nontumoral lesions, and 11 normal control tissues. Results A strong positive staining with the L19 antibody could be observed in 87% of the investigated malignant tumors, in only 38% of the benign tumors, and in 20% of the nontumoral lesions (P <.0001). The extra domain B was completely absent in the normal control tissue samples. Conclusions The results show that ED-B is abundantly expressed around the neovasculature and in the stroma of the majority of malignant tumors of the head and neck but is undetectable in normal tissues. The ED-B domain of fibronectin is a good-quality tumor-stroma,associated antigen that warrants clinical trials with antibody-based pharmaceuticals, including immunoscintigraphic investigations and radioimmunoguided surgery with the radiolabeled L19 antibody. [source]


    Cyclin D1 Amplification and p16(MTS1/CDK4I) Deletion Correlate With Poor Prognosis in Head and Neck Tumors,

    THE LARYNGOSCOPE, Issue 3 2002
    Ali Namazie MD
    Abstract Objectives/Hypothesis Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. Study Design We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. Methods Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. Results Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. Conclusions We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer. [source]


    Sentinel node biopsy and head and neck tumors,Where do we stand today?

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2006
    FCAP, Kenneth O. Devaney MD
    Abstract Background. Sentinel lymph node sampling may be studied profitably in series of patients with 1 tumor type, such as breast carcinoma, in 1 anatomic locale. The present work analyzes the efficacy of sentinel node sampling in a pathologically diverse group of lesions from an anatomically diverse region such as the head and neck; however, there are risks conflating the findings in different tumors with radically different behaviors, in the process producing muddled data. This report reviews the head and neck experience with sentinel sampling and concludes that certain tumor types that have a known propensity for aggressive behavior are the best candidates for trials employing sentinel node sampling; candidates include many cutaneous melanomas of the head and neck, oropharyngeal squamous carcinomas, and selected thyroid carcinomas. Despite the growing popularity of sentinel node sampling in a variety of regions of the body, however, at this juncture this technique remains an investigational procedure, pending demonstration of a tangible improvement in patient outcome through its use. It is recommended that studies of the efficacy of this technique strive, whenever possible, to segregate results of different tumor types in different head and neck locales from one another so as to produce more focused findings for discrete types of malignancies, and not group together tumor types that may in reality exhibit different biological behaviors. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source]


    Particle beam radiotherapy for head and neck tumors: Radiobiological basis and clinical experience

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2006
    Barbara Alicja Jereczek-Fossa MD
    Abstract Background. Head and neck tumors are often located near critical organs, making it impossible to deliver a dose of conventional radiotherapy high enough to eradicate the disease. Our aim was to review the potential benefits and available clinical experience of particle beam therapy (hadrontherapy) in the treatment of these tumors. Methods. A review of the literature was carried out through a MEDLINE search (publications between 1980 and 2005). Results. A review of the available clinical data shows that particle beam therapy can offer several radiobiological and physical advantages over conventional photon radiotherapy: improved dose distribution permits dose escalation within the target and optimal sparing of normal tissue. Preclinical and clinical studies suggest that there may be benefits to using hadrontherapy for tumors characterized by poor radiosensitivity and critical location. At present, the most used hadrons are protons and, as yet on an experimental basis, carbon ions. It is now well accepted that there are certain indications for using proton therapy for skull base tumors (chordoma and chondrosarcoma), paranasal sinus carcinomas, selected nasopharyngeal tumors, and neutron/ion therapy for salivary gland carcinomas (in particular, adenoid cystic tumors). Its viability in other cases, such as locally advanced squamous cell carcinoma, melanoma, soft tissue sarcoma, and bone sarcoma, is still under investigation. Conclusions. Hadrontherapy can be beneficial in the treatment of tumors characterized by poor radiosensitivity and critical location. Further clinical and radiobiological studies are warranted for improved selection of patient population. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source]


    Adenoid cystic carcinoma: A retrospective clinical review

    INTERNATIONAL JOURNAL OF CANCER, Issue 3 2001
    Atif J. Khan M.D.
    Abstract Adenoid cystic carcinoma (ACC) are uncommon tumors, representing about 10% to 15% of head and neck tumors. We compare the survival and control rates at our institution with those reported in the literature, and examine putative predictors of outcome. All patients registered with the tumor registry as having had ACC were identified. Demographic and survival variables were retrieved from the database. Additionally, a chart review of all patients was done to obtain specific information. Minor gland tumors were staged using the American Joint Committee on Cancer's criteria for squamous cell carcinomas in identical sites. Histopathologic variables retrieved included grade of the tumor, margins, and perineural invasion. Treatment modalities, field sizes, and radiation doses were recorded in applicable cases. An effort to retrieve archival tumor specimens for immunohistochemical analysis was undertaken. A total of 69 patients were treated for ACC from 1955 to 1999. One patient, who presented with fatal brain metastasis, was excluded from further analysis. Of the remaining 68 patients, 30 were men and 38 were women. The average age at diagnosis was 52 years, and mean follow-up was 13.2 years. Mean survival was 7.7 years. Overall survival (OS) rates at 5, 10, and 15 years were 72%, 44%, and 34%, and cause-specific survival was 83%, 71%, and 55%, respectively. Recurrence-free survival rates were 65%, 52%, and 30% at 5, 10, and 15 years, with a total of 29 of 68 (43%) eventually suffering a recurrence. Overall survival was adversely affected by advancing T and AJCC stage. Higher tumor grades were also associated with decreased OS, although the numbers compared were small. Primaries of the nasosinal region fared poorly when compared with other locations. Total recurrence-free survival, local and distant recurrence rates were distinctly better in primaries of the oral cavity/oropharynx when compared with those in other locations. Reduced distant recurrence-free survival was significantly associated with increasing stage. No other variables were predictive for recurrence. Additionally, we found that nasosinal tumors were more likely to display higher stage at presentation, and were more often associated with perineural invasion. Also of interest was the association of perineural invasion with margin status, with 15 of 20 patients with positive margins displaying perineural invasion, while only 5 of 17 with negative margins showed nerve invasion (P = 0.02). On immunohistochemistry, 2 cases of the 29 (7%) tumor specimens found displayed HER-2/neu positivity. No correlation between clinical behavior and positive staining could be demonstrated. Our data concur with previous reports on ACC in terms of survival and recurrence statistics. Stage and site of primary were important determinants of outcome. Grade may still serve a role in decision making. We could not demonstrate any differences attributable to primary modality of therapy, perhaps due to the nonrandomization of patients into the various treatment tracks and the inclusion of palliative cases. Similarly, perineural invasion, radiation dose and field size, and HER-2/neu positivity did not prove to be important factors in our experience. © 2001 Wiley-Liss, Inc. [source]


    Demographic and risk factors in patients with head and neck tumors

    JOURNAL OF MEDICAL VIROLOGY, Issue 5 2009
    Ruth Tachezy
    Abstract The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzyme-linked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral-anal contact (P,=,0.02) and tobacco and alcohol use than controls (P,=,0.001; P,=,0.02, respectively). High-risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P,<,0.0001). The association between the presence of high-risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P,<,0.0001). The prevalence of HPV-specific antibodies was significantly higher in cases than in controls (adjusted P,<,0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR,=,44.3, P,<,0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high-risk HPV DNA in oral exfoliated cells and HPV-specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV-associated head and neck cancer, with a high sensitivity (83%) and specificity (88%). J. Med. Virol. 81:878,887, 2009. © 2009 Wiley-Liss, Inc. [source]


    Microimaging FTIR of head and neck tumors.

    MICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2009

    Abstract On continuing our studies on head and neck neoplasia, specimens from salivary gland tumors have been explored by using infrared microimaging spectroscopy to discern healthy from neoplastic tissues. Samples with Warthin tumor, epithelial displasia, marginal B-cell lymphoma, low-grade adenocarcinoma, and adenoid cystic carcinoma pathologies have been investigated by using conventional light sources. Changes were monitored at the molecular level, probing spectral markers such as Amide I and II, phosphate, nucleic acids, and carbohydrates vibrational modes. In all cases, supervised and unsupervised spectral analyses resulted in satisfactory agreement with histopathological findings. Microsc. Res. Tech., 2009. © 2008 Wiley-Liss, Inc. [source]


    111Indium Pentetreotide Imaging in the Evaluation of Head and Neck Tumors

    THE LARYNGOSCOPE, Issue 10 2005
    David Myssiorek MD
    Abstract Objectives/Hypothesis: Peptide receptor imaging with 111Indium pentetreotide is useful in the diagnosis of diffuse neuroendocrine system tumors (DNEST) of the head and neck. Uses of 111Indium pentetreotide scintigraphy include tumor and metastases detection, familial tumor screening, and surveillance for recurrence. Using target to background ratios (TBR) could generate a comparative scale for these tumors. Study Design: A retrospective study evaluated the size, TBR, conventional imaging, and outcomes of patients imaged with 111Indium pentetreotide scintigraphy for suspected head and neck DNEST. Methods: Patients with head and neck tumors imaged by 111Indium pentetreotide scintigraphy during a nine-year period were reviewed. Data analyzed were age, sex, scintigraphy, pathology, and conventional radiology. Tumor data included dimension, multiplicity, metastases, and tumor and brain counts. Results: Fifty-three patients underwent 58 scans. The sensitivity and specificity were 93% and 92%. Several different DNEST were successfully evaluated, including familial paragangliomas and multiple paragangliomas. TBRs were variable depending on type of DNEST. Conclusions:111Indium pentetreotide scintigraphy is accurate in determining the presence of paragangliomas, carcinoid tumors, esthesioneuroblastomas, small cell neuroendocrine tumors, andmetastases. It is an excellent surveillance tool. Screening patients for familial paragangliomas can be accomplished. No reliable comparative scale to distinguish amongst the various DNEST could be developed using TBR. [source]


    Dominant Negative p63 Isoform Expression in Head and Neck Squamous Cell Carcinoma,

    THE LARYNGOSCOPE, Issue 12 2004
    Joseph C. Sniezek MD
    Abstract Objectives/Hypothesis: p63, a member of the p53 family of genes, is vital for normal epithelial development and may play a critical role in epithelial tumor formation. Although p63 has been identified in various head and neck malignancies, a detailed analysis of which of the six isoforms of the p63 gene is present in normal mucosa and head and neck malignancies has not yet been performed. The study analyzed p63 isoform expression on the RNA and protein level in normal, diseased, and malignant mucosa of the head and neck to examine the differential expression of p63 isoforms in head and neck tumors versus adjacent nonmalignant tissue and to identify the predominant p63 isoform expressed in head and neck squamous cell carcinoma (HNSCC). Study Design: Three experiments were performed. In experiment 1, p63 expression was analyzed by immunohistochemical analysis in 36 HNSCC specimens and matched normal tissue control specimens harvested from the same patient. Western blot analysis was also performed on matched specimens to confirm the identity of the p63 isoforms that were found. In experiment 2, reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed on matched normal and tumor specimens to analyze and quantitatively compare p63 isoform expression at the RNA level. In experiment 3, p63 expression was evaluated by immunohistochemical analysis in oral lichen planus, a benign mucosal lesion marked by hyperdifferentiation and apoptosis. Methods: Immunohistochemical analysis, RT-PCR, and Western blot analysis of p63 were performed on HNSCC specimens and matched normal tissue control specimens. p63 expression in oral lichen planus specimens was also examined by immunohistochemical analysis. Results: In experiment 1, analysis of 36 HNSCC specimens from various head and neck subsites showed p63 expression in all tumors and matched normal tissue specimens (36 of 36). Western blot analyses indicated that dominant negative (,N) isoform p63, (,Np63,) is the major isoform expressed at the protein level in tumors and adjacent normal tissue. In experiment 2, RT-PCR analyses of 10 matched specimens confirmed that, although all three ,Np63 isoforms (,Np63,, ,Np63,, and ,Np63,) are expressed in normal and malignant mucosa of the head and neck, ,Np63, is the predominant transcript expressed. In experiment 3, immunohistochemical analysis of p63 in the pro-apoptotic condition of lichen planus indicated that p63 is underexpressed as compared with normal mucosal specimens. Conclusion: Although all three ,Np63 isoforms are present in HNSCC, ,Np63, protein is the predominant isoform expressed in these malignancies. ,Np63, is also overexpressed in tumors compared with matched normal tissue specimens and is underexpressed in the pro-apoptotic condition of lichen planus. These findings suggest that ,Np63, plays an anti-differentiation and anti-apoptotic role in the mucosal epithelium of the head and neck, possibly playing a pivotal role in the formation of HNSCC. Currently, ,Np63, is an attractive target for mechanistic study aimed at therapeutic intervention. [source]


    Candidate's Thesis: The Application of Sentinel Node Radiolocalization to Solid Tumors of the Head and Neck: A 10-Year Experience,

    THE LARYNGOSCOPE, Issue 1 2004
    James C. Alex MD
    Abstract Objectives/Hypothesis The goals of the research study were to develop an easily mastered, accurate, minimally invasive technique of sentinel node radiolocalization with biopsy (SNRLB) in the feline model; to compare it with blue-dye mapping techniques; and to test the applicability of sentinel node radiolocalization biopsy in three head and neck tumor types: N0 malignant melanoma, N0 Merkel cell carcinoma, and N0 squamous cell carcinoma. Study Design Prospective consecutive series studies were performed in the feline model and in three head and neck tumor types: N0 malignant melanoma (43 patients), N0 Merkel cell carcinoma (8 patients), and N0 squamous cell carcinoma (20 patients). Methods The technique of sentinel node radiolocalization with biopsy was analyzed in eight felines and compared with blue-dye mapping. Patterns of sentinel node gamma emissions were recorded. Localization success rates were determined for blue dye and sentinel node with radiolocalization biopsy. In the human studies, all patients had sentinel node radiolocalization biopsy performed in a similar manner. On the morning of surgery, each patient had sentinel node radiolocalization biopsy of the sentinel lymph node performed using an intradermal or peritumoral injection of technetium Tc 99m sulfur colloid. Sentinel nodes were localized on the skin surface using a handheld gamma detector. Gamma count measurements were obtained for the following: 1) the "hot" spot/node in vivo before incision, 2) the hot spot/node in vivo during dissection, 3) the hot spot/node ex vivo, 4) the lymphatic bed after hot spot/node removal, and 5) the background in the operating room. The first draining lymph node(s) was identified, and biopsy of the node was performed. The radioactive sentinel lymph node(s) was submitted separately for routine histopathological evaluation. Preoperative lymphoscintigrams were performed in patients with melanoma and patients with Merkel cell carcinoma. In patients with head and neck squamous cell carcinoma, the relationship between the sentinel node and the remaining lymphatic basin was studied and all patients received complete neck dissections. The accuracy of sentinel node radiolocalization with biopsy, the micrometastatic rate, the false-negative rate, and long-term recurrence rates were reported for each of the head and neck tumor types. In the melanoma study, the success of sentinel node localization was compared for sentinel node radiolocalization biopsy, blue-dye mapping, and lymphoscintigraphy. In the Merkel cell carcinoma study, localization rates were evaluated for sentinel node radiolocalization biopsy and lymphoscintigraphy. In the head and neck squamous cell carcinoma study, the localization rate of sentinel node radiolocalization biopsy and the predictive value of the sentinel node relative to the remaining lymphatic bed were determined. All results were analyzed statistically. Results Across the different head and neck tumor types studied, sentinel node radiolocalization biopsy had a success rate approaching 95%. Sentinel node radiolocalization biopsy was more successful than blue-dye mapping or lymphoscintigraphy at identifying the sentinel node, although all three techniques were complementary. There was no instance of a sentinel node-negative patient developing regional lymphatic recurrence. In the head and neck squamous cell carcinoma study, there was no instance in which the sentinel node was negative and the remaining lymphadenectomy specimen was positive. Conclusion In head and neck tumors that spread via the lymphatics, it appears that sentinel node radiolocalization biopsy can be performed with a high success rate. This technique has a low false-negative rate and can be performed through a small incision. In head and neck squamous cell carcinoma, the histological appearance of the sentinel node does appear to reflect the regional nodal status of the patient. [source]


    Expression of the Extra Domain B of Fibronectin, a Marker of Angiogenesis, in Head and Neck Tumors,

    THE LARYNGOSCOPE, Issue 7 2003
    Manfred T. Birchler MD
    Abstract Objectives/Hypothesis The extra domain B (ED-B) of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is expressed in the majority of aggressive solid human tumors, whereas it is not detectable in normal vessels and tissues. Study Design In view of the diagnostic and therapeutic clinical applications of the L19 antibody, which is specific for the ED-B domain of fibronectin, a prospective immunohistochemical analysis of different head and neck tumors was performed. Methods In all, 82 head and neck tissue biopsy specimens were immunohistochemically analyzed using the L19 antibody. They consisted of 53 different malignant tumors, 8 benign tumors, 10 nontumoral lesions, and 11 normal control tissues. Results A strong positive staining with the L19 antibody could be observed in 87% of the investigated malignant tumors, in only 38% of the benign tumors, and in 20% of the nontumoral lesions (P <.0001). The extra domain B was completely absent in the normal control tissue samples. Conclusions The results show that ED-B is abundantly expressed around the neovasculature and in the stroma of the majority of malignant tumors of the head and neck but is undetectable in normal tissues. The ED-B domain of fibronectin is a good-quality tumor-stroma,associated antigen that warrants clinical trials with antibody-based pharmaceuticals, including immunoscintigraphic investigations and radioimmunoguided surgery with the radiolabeled L19 antibody. [source]


    Pulmonary Function After Pectoralis Major Myocutaneous Flap Harvest

    THE LARYNGOSCOPE, Issue 3 2002
    FACS, Yoav P. Talmi MD
    Abstract Objective The pectoralis major myocutaneous flap is widely used in the reconstruction of surgical defects in the head and neck region. Pulmonary atelectasis has been reported in patients undergoing these procedures, and many of these patients are heavy smokers and drinkers and have associated cardiopulmonary disorders. Flap harvest and donor site closure may lead to impairment of pulmonary function before and after the use of pectoralis major myocutaneous (PMC) in surgical reconstruction in patients with cancer of the head and neck. Methods Patients undergoing extirpation of head and neck tumors with PMC reconstruction were prospectively evaluated. Patient age, smoking history (pack-years), anesthesia duration, percentage predicted pre- and postoperative FEV1, percentage-predicted pre- and postoperative FVC (forced vital capacity), and preoperative SaO2 (oxygen saturation) were evaluated. Preoperative FEV1/FVC ratio was calculated. Chest x-rays were reviewed. Results Only 11 patients, 5 of whom smoked, could be evaluated postoperatively. Preoperative FEV1/FVC was more than 70 and FEV1 more than 75% predicted in all patients. A decrease in FVC was observed in 7 of the 11 patients, which ranged between 2% and 27% without any clinically obvious respiratory manifestations. A baseline SaO2 of more than 96% was noted in all patients. Four of 9 postoperative chest x-rays demonstrated atelectasis. Conclusions PMC harvest and donor site closure may lead to the recorded decrease in FVC measurements. These changes did not manifest clinically. Nevertheless, alternative methods of surgical defect closure should be considered in patients with severe preexisting pulmonary disorders. [source]


    Cyclin D1 Amplification and p16(MTS1/CDK4I) Deletion Correlate With Poor Prognosis in Head and Neck Tumors,

    THE LARYNGOSCOPE, Issue 3 2002
    Ali Namazie MD
    Abstract Objectives/Hypothesis Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. Study Design We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. Methods Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. Results Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. Conclusions We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer. [source]


    Gene Therapy for Head and Neck Cancer ,

    THE LARYNGOSCOPE, Issue 5 2000
    Lyon L. Gleich MD
    Abstract Objectives/Hypothesis New treatment methods are needed for head and neck cancer to improve survival without increasing morbidity. Gene therapy is a potential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology and treatment strategies. Given the current technological vector limitations in transmitting the therapeutic genes, treatments that require the fewest number of cells to be altered by the new gene are optimal. Therefore an immune-based gene therapy strategy was selected in which the tumors were transfected with the gene for an alloantigen, human leukocyte antigen (HLA),B7, a class I major histocompatibility complex (MHC). This would restore an antigen presentation mechanism in the tumor to induce an antitumor response. This gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design Prospective trial. Methods Twenty patients with advanced head and neck cancer who had failed conventional therapy and did not e-press HLA-B7 were treated with gene therapy using a lipid vector by direct intratumoral injection. The gene therapy product contained the HLA-B7 gene and the ,2-microglobulin gene, which permits complete e-pression of the class I MHC at the cell surface. Patients were assessed for any adverse effects, for changes in tumor size, for time to disease progression, and for survival. Biopsy specimens were assessed for pathological response, HLA-B7 e-pression, apoptosis, cellular proliferation, CD-8 cells, granzyme, and p53 status. Results There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a partial response and two patients had stable disease. Two of the tumors completely responded clinically, but tumor was still seen on pathological examination. The time to disease progression in the responding patients was 20 to 80 weeks. The median survival in patients who completed gene therapy was 54 weeks, compared with 21 weeks in patients whose tumors progressed after the first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA-B7 was demonstrated in the treated tumors, and increased apoptosis was seen in the responding tumors. Conclusion Significant advances have been made in the field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in the treatment of cancer and can induce tumor responses in head and neck tumors. Alloantigen gene therapy has significant potential as an adjunctive treatment of head and neck cancer. [source]


    Avoiding Transfusion in Head and Neck Surgery: Feasibility Study of Erythropoietin,

    THE LARYNGOSCOPE, Issue 1 2000
    Erich M. Sturgis MD
    Abstract Objective: To determine the feasibility of perioperative erythropoietin to avoid blood transfusion in head and neck cancer surgery. Study Design: Retrospective chart review. Methods: Ninety-nine patients undergoing surgical resection of head and neck tumors at our institution were assessed for demographic data, nutritional parameters, tumor/surgical information, hematological/transfusion data, and contraindications to erythropoietin. Each transfusion was classified as to its appropriateness, and the potential benefit of erythropoietin was assessed in each patient. A cost analysis was also performed. Results: Most transfused patients (63%) received too many units. A subgroup at high risk of transfusion was identified who would benefit most from perioperative erythropoietin. Assuming that perioperative erythropoietin therapy is equivalent to the transfusion of 4 units, we estimate that the majority (74%) of transfused patients would not have required a transfusion if more stringent transfusion criteria were followed and those at high risk were given perioperative erythropoietin. Although the cost for transfusing 4 units is equivalent to that of a perioperative course of erythropoietin, the overall direct cost of erythropoietin treatment would actually have been more expensive. Conclusions: Perioperative erythropoietin therapy may be appropriate for a subgroup of head and neck cancer patients, but a prospective randomized controlled study in such a subgroup is needed to better define those most likely to benefit from it and to assess actual cost/benefit ratios. [source]


    Heparanase as a molecular target of cancer chemotherapy

    CANCER SCIENCE, Issue 7 2004
    Siro Simizu
    Cancer cells require the ability to degrade the extracellular matrix (ECM) in order to turn into invasive and metastatic cancer cells. Many proteases and glycosidases are essential in the process of dissolving the components of the ECM. An endo-,-D-glucuronidase, heparanase, is capable of specifically degrading one of the ECM components, heparan sulfate, and this activity is associated with the metastatic potential of tumor cells. Since heparanase mRNA is overexpressed in many human tumors (e.g., hepatomas, head and neck tumors, and esophageal carcinomas), the mechanisms regulating the activity of heparanase should be clarified; considering the possible role of heparanase in cancer, the development of heparanase inhibitors would appear to be advantageous. This review will focus on recent findings that have contributed to the characterization of heparanase and to the elucidation of the transcriptional regulation of heparanase mRNA expression, as well as the development of heparanase inhibitors. [source]